公开(公告)号：EP1912997B1

公开(公告)日：2011-09-14

申请号：EP06764267.8

申请日：2006-07-28

申请人： Tibotec Pharmaceuticals ,  Medivir Aktiebolag

发明人： RABOISSON, Pierre, Jean-Marie, Bernard ,  DE KOCK, Herman, Augustinus ,  HU, Lili ,  SURLERAUX, Dominique, Louis, Nestor, Ghislain ,  SIMMEN, Kenneth, Alan ,  SALVADOR ODÉN, Lourdes, ,  NILSSON, Karl, Magnus, ,  ROSENQUIST, Åsa Annica Kristina, ,  SAMUELSSON, Bengt Bertil,

IPC分类号： C07D487/04 ,  C07D245/04 ,  C07K5/078 ,  A61K38/05 ,  A61K31/33 ,  A61P31/14 ,  C07K5/06

CPC分类号： C07D487/04 ,  C07D245/04 ,  C07K5/06139

摘要： Inhibitors of HCV replication of formula (I), and the N-oxides, salts, and stereoisomers thereof, wherein each dashed line represents an optional double bond; X is Ν, CH and where X bears a double bond it is C; R1a and R1b are hydrogen, C3-7cycloalkyl, aryl, Het, C1-6alkoxy, C1-6alkyl optionally substituted with halo, C1-6alkoxy, cyano, polyhaloC11-6alkoxy, C3-7cycloalkyl, aryl, or with Het; or R1a and R1b together with the nitrogen to which they are attached form a 4 to 6 membered heterocyclic ring which may be optionally substituted; L is a direct bond, -O- , -O-C1-4alkanediyl-, -O-CO-, -O-C(=O)-ΝR5a - or -O -C(=O)-NR5a-C1-4alkanediyl-; R2 is hydrogen, and where X is C or CH, R2 may also be C1-6alkyl; R3 is hydrogen, C1-6alkyl, C1-6alkoxyC1-6alkyl, C3-7cycloalkyl, amino, mono- or diC1-6alkylamino; R4 is aryl or a saturated, a partially unsaturated or completely unsaturated 5 or 6 membered monocyclic or 9 to 12 membered bicyclic heterocyclic ring system wherein said ring system contains one nitrogen, and optionally one to three additional heteroatoms selected from O, S and N, and wherein the remaining ring members are carbon atoms; wherein said ring system may be optionally substituted; n is 3, 4, 5, or 6; p is 1 or 2; aryl is phenyl, naphthyl, indanyl, or 1,2,3,4-tetrahydronaphthyl, each of which may be optionally substituted with one, two or three substituents; and Het is a 5 or 6 membered saturated, partially unsaturated or completely unsaturated heterocyclic ring containing 1 to 4 heteroatoms selected from N, O and S , being optionally condensed with a benzene ring, and wherein Het may be optionally substituted with one, two or three substituents; pharmaceutical compositions containing compounds (I) and processes for preparing compounds (I).

摘要翻译： 式（I）的HCV复制抑制剂及其N-氧化物，盐和立体异构体，其中每个虚线表示任选的双键; X是N，CH，并且其中X带有双键，它是C; R 1a和R 1b是氢，C 3-7环烷基，芳基，Het，C 1-6烷氧基，任选被卤素，C 1-6烷氧基，氰基，多卤代C 1-6烷氧基，C 3-7环烷基，芳基或与Het取代的C 1-6烷基; 或者R1a和R1b与它们所连接的氮一起形成可任选被取代的4至6元杂环; L是直接键，-O - ， - OC 1-4烷烃二基 - ， - O-CO-，-O-C（= O）-NR 5a - 或-O-C（= O）-NR 5a -C 1-4链烷二基 - R2是氢，并且其中X是C或CH，R2也可以是C1-6烷基; R 3是氢，C 1-6烷基，C 1-6烷氧基C 1-6烷基，C 3-7环烷基，氨基，单或二C 1-6烷基氨基; R 4是芳基或饱和的，部分不饱和的或完全不饱和的5或6元单环或9-12元双环杂环系统，其中所述环系统含有一个氮和任选1-3个选自O，S和N的另外的杂原子， 并且其中剩余的环成员是碳原子; 其中所述环系可以任选被取代; n是3,4,5或6; p是1或2; 芳基是苯基，萘基，茚满基或1,2,3,4-四氢萘基，它们中的每一个可以任选地被一个，两个或三个取代基取代; 并且Het是含有1至4个选自N，O和S的杂原子的5或6元饱和，部分不饱和或完全不饱和的杂环，其任选地与苯环稠合，并且其中Het可以任选被一个，两个或三个 三个取代基; 含有化合物（I）的药物组合物和用于制备化合物（I）的方法。